- In CMV seropositive adults with severe sepsis or trauma , pulmonary and systemic CMV reactivation amplifies and perpetuates both lung and systemic inflammation mediated through specific cytokines, and contributes to pulmonary injury and multiorgan system failure,

AND

- Prevention of CMV reactivation with ganciclovir decreases pulmonary and systemic inflammatory cytokines that are important in the pathogenesis of sepsis and trauma related complications.

For first 5 days, dosing of intravenous ganciclovir is 10 mg/kg daily, given as 5 mg/kg every 12 hours (adjusted for renal function). After first 5 days (up to 28 days) IV ganciclovir 5 mg/kg QD ( adjusted for renal function). A minimum interval of 6 hours is required between the first and second dose.

Other Name: IV Ganciclovir

Placebo Comparator: Placebo

Drug: Placebo

For first 5 days, dosing of intravenous placebo is daily, given every 12 hours. After first 5 days (up to 28 days), IV placebo QD. A minimum interval of 6 hours is required between the first and second dose.

The placebo is an IV solution that does not contain any active medications.

FDA licensed test in a local lab approved by the coordinating center (FHCRC, Seattle, WA).

Test in central study lab (ARUP, Salt Lake City, UT)

A report that patient has previously been tested and found to be CMV seropositive at any time (a credible next of kin report is acceptable; confirmatory test will be done but results are not required for randomization)

Severe sepsis criteria (as defined in appendix G) within a 24-hour time period within the 120 hour window

OR

Trauma with respiratory failure and an ISS score > 15 within a 24 hour time period, and within the 120 hour window (where mechanical ventilation is not due solely to a head injury)

On the day of randomization (by local criteria):

Not eligible for SBT (use of sedation and/or vasopressor does not specifically contraindicate SBT),or

Failed SBT

Exclusion Criteria:

BMI > 60 (1st weight during hospital admission)

Known or suspected immunosuppression, including:

HIV+ (i.e. prior positive test or clinical signs of suspicion of HIV/AIDS; a negative HIV test is not required for enrollment)

stem cell transplantation:

within 6 months after autologous transplantation or

within 1 years after allogeneic transplantation (regardless of immunosuppression)

greater than 1 year of allogeneic transplantation if still taking systemic immunosuppression or prophylactic antibiotics (e.g. for chronic graft versus host disease)

Note: if details of stem cell transplantation are unknown, patients who do not take systemic immunosuppression and do not take anti-infective prophylaxis are acceptable for enrollment and randomization.

Note: if no information on these agents is available in the history and no direct or indirect evidence exists from the history that any condition exists that requires treatment with these agents (based on the investigator's assessment), the subject may be enrolled. For all drug information, next-of-kin estimates are acceptable. See Appendix D for commonly prescribed immunosuppressive agents.

Expected to survive < 72 hours (in the opinion of the investigator)

Has been hospitalized for > 120 hours (subjects who are transferred from a chronic care ward, such as a rehabilitation unit, with an acute event are acceptable).

Pregnant or breastfeeding (either currently or expected within one month).

Note: for women of childbearing age (18-60 years, unless documentation of surgical sterilization [hysterectomy, tubal ligation, oophorectomy]), if a pregnancy test has not been done as part of initial ICU admission work-up, it will be ordered stat and documented to be negative before randomization. Both urine and blood tests are acceptable.

Use of cidofovir within seven (7) days of patient randomization. The use of the following antivirals is permitted under the following conditions:

Ganciclovir, foscarnet, high-dose acyclovir, or valacyclovir until the day of randomization

Acyclovir as empiric therapy for central nervous system HSV or VZV infection until the diagnosis can be excluded

For enrolled patients during the active study drug phase, acyclovir, famciclovir, valacyclovir for treatment of HSV or VZV infection as clinically indicated.

Currently enrolled in an interventional trial of an investigational therapeutic agent known or suspected to have anti-CMV activity, or to be associated with significant known hematologic toxicity (Note: confirm eligibility with one of the study medical directors at the coordinating site).

At baseline patients who have both a tracheostomy, and have been on continuous 24-hour chronic mechanical ventilation.

Patients with Child Class C Cirrhosis.

Patients with pre-existing interstitial lung disease.

Contacts and Locations

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study.
To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below.
For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01335932